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Two parameters in high-frequency ultrasound (20-80 MHz) have been found to be sensitive to a range of pathologies in resected margins from breast conservation surgery: The number of peaks (the peak density) in the waveform spectrum and the slope of the Fourier transform of the waveform spectrum. Previous studies have indicated that peak density and slope may correlate to microscopic heterogeneity in tissue structure, which is modified by atypical and malignant processes. To test this hypothesis, through-transmission and pulse-echo measurements were acquired from gelatin-based phantoms containing polyethylene microspheres and nylon fibers (2.5-10% volume concentration). Multipole methods were also used to model through-transmission measurements of tumor progression in lobular carcinoma in situ. The simulated breast tissue contained 1000-2000 nucleated cells with random lobular cavities. The peak densities of the heterogeneous phantoms were significantly greater than those of the homogeneous control samples, whereas the slopes were less. Similarly, the models produced spectra with peak densities that increased with malignant cell proliferation. The results are consistent with breast tissue data, and provide a physical mechanism for the use of peak density and slope in the imaging of breast tissues with atypical and malignant pathologies. This work was supported by Utah Valley University.

High-frequency (20-80 MHz) ultrasonic measurements have the potential to detect cancer and other pathologies within breast tissues in real time, and thus may assist surgeons in obtaining negative or cancer free margins during lumpectomy. To study this approach, ultrasonic tests were performed on 34 lumpectomy margins and other breast tissue specimens from 17 patients to provide pulse-echo and through-transmission waveforms. Time-domain waveform analysis yielded ultrasonic attenuation, while fast Fourier transforms of the waveforms produced first- and second-order ultrasonic spectra. A multivariate analysis of the parameters derived from these data permitted differentiation of normal, adipose, benign, and malignant breast pathologies. The results provide a strong correlation between tissue microstructure and ultrasonic parameters relative to the morphology and stiffness of microscopic features such as ductules, lobules, and fibrous structures. Ultrasonic testing of bovine heart, liver, and kidney tissues supports this correlation, showing that tissues having stiff fiber-like or filled-duct structures, such as myocardium or ductal carcinomas, display greater peak densities in the ultrasonic spectra than tissues with soft, open duct-like structures, such as kidney tissue or normal breast glands. The sensitivity of high-frequency ultrasound to histopathology may assist in eliminating invasive re-excision for lumpectomy patients. [Work supported by NIH R21CA131798.]